JP2577016B2 - Gastrointestinal disease treatment - Google Patents
Gastrointestinal disease treatmentInfo
- Publication number
- JP2577016B2 JP2577016B2 JP29156387A JP29156387A JP2577016B2 JP 2577016 B2 JP2577016 B2 JP 2577016B2 JP 29156387 A JP29156387 A JP 29156387A JP 29156387 A JP29156387 A JP 29156387A JP 2577016 B2 JP2577016 B2 JP 2577016B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- disease treatment
- gastrointestinal disease
- gastric
- hydrochloric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 〈産業上の利用分野〉 本発明は、２−フェニル−1,2−ベンゾイソセレナゾ
ール−３（2H）−オン（以下、化合物Ａと称す）又はそ
の生理学的許容塩を含有する消化管疾患の予防および治
療剤に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to 2-phenyl-1,2-benzisoselenazol-3 (2H) -one (hereinafter referred to as compound A) or a physiologically acceptable substance thereof. The present invention relates to a prophylactic and therapeutic agent for a gastrointestinal tract disease containing a salt.
〈従来の技術〉 従来の消化管疾患用剤としては、制酸剤、抗コリン剤
およびH2ブロッカー等の胃液分泌抑制剤、粘膜防御因子
賦活剤等をあげることができる。しかしながら、これら
の薬剤は未だ臨床的に充分満足できるものではない。The <Prior Art> conventional gastrointestinal disorders for agents include antacids, anticholinergic agents and H 2 gastric secretion inhibitors such as blockers, mucosal protective factor enhancer like. However, these drugs are not yet clinically satisfactory.
化合物Ａはグルタチオンペルオキシダーゼ様抗酸化作
用および抗炎症作用を有することが知られている（バイ
オケミカル ファーマコロジーVol.33 NO.20 3235−323
9,3241−3245（1984））。Compound A is known to have glutathione peroxidase-like antioxidant and anti-inflammatory effects (Biochemical Pharmacology Vol. 33 NO.20 3235-323).
9,3241-3245 (1984)).
しかしながら、かかる作用は消化管疾患の治療及び予
防効果と関連性を有するものではない。However, such effects are not related to the therapeutic and preventive effects of gastrointestinal diseases.
〈発明が解決しようとする問題点〉 本発明者らは、新規な消化管疾患の治療剤を見いだす
べく鋭意検討した結果、本発明を完成した。<Problems to be Solved by the Invention> The present inventors have conducted intensive studies to find a novel therapeutic agent for gastrointestinal diseases, and as a result, completed the present invention.
〈発明の構成〉 本発明は、化合物Ａ又はその生理学的許容塩を有効成
分とする消化管疾患の予防及び治療剤に関する。<Constitution of the Invention> The present invention relates to a prophylactic and therapeutic agent for gastrointestinal diseases comprising Compound A or a physiologically acceptable salt thereof as an active ingredient.
本発明にかかわる消化管疾患としては、食道炎、食道
潰瘍、胃炎、胃潰瘍、十二指腸潰瘍、腸炎、胃腸管出血
等をあげることができ、中でも好ましい治療効果を期待
しうるものとして胃炎、胃潰瘍、十二指腸潰瘍等をあげ
ることができる。Gastrointestinal diseases according to the present invention include esophagitis, esophageal ulcer, gastritis, gastric ulcer, duodenal ulcer, enteritis, gastrointestinal bleeding and the like. Ulcers and the like.
本発明にかかわる化合物Ａは、賦形剤、結合剤、崩壊
剤、溶解剤等の添加剤と共に公知の製剤技術により錠
剤、カプセル剤、散剤、顆粒剤、シロップ剤、注射剤等
の剤型とすることができる。製剤の具体的処方例を下記
に示す。Compound A according to the present invention can be used in the form of tablets, capsules, powders, granules, syrups, injections and the like by known preparation techniques together with additives such as excipients, binders, disintegrants, and dissolving agents. can do. Specific examples of the formulation are shown below.
錠剤 化合物Ａ 50mg カルボキシメチルセルロース 25mg でんぷん 5mg 結晶セルロース 40mgステアリン酸マグネシウム 2mg 計 122mg 化合物Ａは通常経口又は非経口投与される。化合物Ａ
の投与量は、経口投与の場合成人１人当たり通常100〜2
000mg/日、好ましくは200〜1000mg/日の範囲であり、患
者の症状に応じて適宜増減すればよい。Tablets Compound A 50 mg Carboxymethyl cellulose 25 mg Starch 5 mg Crystalline cellulose 40 mg Magnesium stearate 2 mg Total 122 mg Compound A is usually orally or parenterally administered. Compound A
The dose is usually 100 to 2 per adult for oral administration
It is 000 mg / day, preferably in the range of 200 to 1000 mg / day, and may be appropriately increased or decreased according to the patient's symptoms.
化合物Ａの毒性は、マウスおよびラットに経口又は腹
腔内投与で検討した結果、下記のLD50（mg/kg）値で示
されている通り極めて低毒性のものであり、又高用量投
与時の所見として、副作用的に問題となるものは認めら
れなかった。The toxicity of Compound A was very low toxicity as shown by the following LD 50 (mg / kg) as a result of oral or intraperitoneal administration to mice and rats. No findings showed any adverse side effects.
〈発明の効果〉 化合物Ａは胃粘膜障害モデルにおける胃粘膜壊死形成
を有意かつ著明に抑制した。従って、化合物Ａは消化管
疾患の予防及び治療剤として優れたものである。 <Effect of the Invention> Compound A significantly and markedly suppressed the formation of gastric mucosal necrosis in a gastric mucosal injury model. Therefore, Compound A is excellent as an agent for preventing and treating gastrointestinal diseases.
以下、本発明を実施例により説明するが、本発明はこ
れに限定されるものではない。Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited thereto.
実施例１ アルコールによる胃粘膜壊死形成に対する化合物Ａの効
果 Sprague−Dawley系ラット（６週令，体重160〜180g,
雄）を24時間絶食後、実験に供した。胃粘膜壊死は塩酸
−アルコール（60％エタノール−150mM塩酸液）1mlを経
口投与することにより惹起した（K.Takeuchi,et al.,Ja
pan.J.Pharmacol.44,269−281（1987）参照）。Example 1 Effect of compound A on gastric mucosal necrosis formation by alcohol Sprague-Dawley rats (6 weeks old, weighing 160-180 g,
Male) was fasted for 24 hours and then subjected to experiments. Gastric mucosal necrosis was induced by oral administration of 1 ml of hydrochloric acid-alcohol (60% ethanol-150 mM hydrochloric acid solution) (K. Takeuchi, et al., Ja.
pan. J. Pharmacol. 44 , 269-281 (1987)).
化合物Ａは0.5gカルボキシメチルセルロース水溶液
（以下、0.5％CMC）に懸濁し、10、30または100mg/kgの
投与量で胃粘膜障害惹起30分前に経口投与した。投与液
量は5ml/kgに一定し、病態対照群には同量の0.5％CMCの
みを経口投与した。Compound A was suspended in a 0.5 g carboxymethylcellulose aqueous solution (hereinafter, 0.5% CMC) and orally administered at a dose of 10, 30, or 100 mg / kg 30 minutes before induction of gastric mucosal injury. The dose was fixed at 5 ml / kg, and the disease control group was orally administered only the same amount of 0.5% CMC.
塩酸−アルコール投与一時間後に、動物をエーテル麻
酔下で放血致死せしめ、胃を摘出した。直ちに３％緩衝
ホルマリン液8mlを胃内に注入した後、同ホルマリン液
中に30分前後浸漬し軽固定した。固定終了後、大弯に沿
って切開し、胃粘膜に生じた壊死病変部の長さ（mm）を
ノギスで計測して一匹当りの総和を病変指数とした。結
果を表２に示した。One hour after the administration of hydrochloric acid-alcohol, the animals were bled to death under ether anesthesia and the stomach was removed. Immediately after injecting 8 ml of a 3% buffered formalin solution into the stomach, it was immersed in the formalin solution for about 30 minutes and lightly fixed. After completion of the fixation, an incision was made along the greater curvature, and the length (mm) of the necrotic lesion formed on the gastric mucosa was measured with a vernier caliper, and the total per animal was defined as the lesion index. The results are shown in Table 2.
上表から明らかなように、塩酸−アルコールによる胃
粘膜壊死モデルにおいて、化合物Ａの前処置により病変
形成は有意かつ用量依存的に抑制された。また、100mg/
kg投与時の病変形成抑制効果は極めて強力であり、抑制
率は94％に達した。 As is clear from the above table, in the gastric mucosal necrosis model using hydrochloric acid-alcohol, lesion treatment was significantly and dose-dependently suppressed by Compound A pretreatment. Also, 100mg /
The effect of suppressing the formation of lesions at the time of kg administration was extremely strong, and the suppression rate reached 94%.
実施例２ 0.6N塩酸による胃粘膜壊死形成に対する化合物Ａの効果 Sprague−Dawley系ラット（７週令，体重170〜200g、
雄）を24時間絶食し、実験に供した。胃粘膜壊死は0.6N
塩酸1mlを投与することにより惹起した（K.Takeuti,et
al.,Japan.J.Pharmacol.44,335−344（1987）参照）。Example 2 Effect of Compound A on Gastric Mucosal Necrosis Formation by 0.6N Hydrochloric Acid Sprague-Dawley rats (7 weeks old, weighing 170-200 g,
Male) was fasted for 24 hours and subjected to experiments. 0.6N gastric mucosal necrosis
It was induced by administering 1 ml of hydrochloric acid (K. Takeuti, et.
al., Japan. J. Pharmacol. 44 , 335-344 (1987)).
化合物Ａは0.5％CMCに懸濁し、10、30または300mg/kg
の投与量で胃粘膜障害惹起30分前に経口投与した。投与
液量は5ml/kgに一定し、病態対照群には同量の0.5％CMC
のみを経口投与した。Compound A is suspended in 0.5% CMC and 10, 30, or 300 mg / kg
Was orally administered 30 minutes before the induction of gastric mucosal injury. The dose was constant at 5 ml / kg, and the same amount of 0.5% CMC was used for the disease control group.
Only was administered orally.
0.6N塩酸投与１時間後に、動物をエーテル麻酔下で放
血致死せしめ、胃を摘出した。直ちに、３％緩衝ホルマ
リン液8mlを胃内に注入した後、同ホルマリン液中に30
分間前後浸漬し軽固定した。固定終了後、実施例１の場
合と同様に胃粘膜に生じた壊死病変部の長さを計測し、
病変指数とした。結果を表３に示した。One hour after administration of 0.6N hydrochloric acid, the animals were sacrificed by exsanguination under ether anesthesia, and the stomach was removed. Immediately after injecting 8 ml of 3% buffered formalin solution into the stomach, 30 ml
It was immersed for about a minute and fixed lightly. After the fixation, the length of the necrotic lesion generated on the gastric mucosa was measured in the same manner as in Example 1,
The lesion index was used. The results are shown in Table 3.
上表から明らかなように、0.6N塩酸による胃粘膜壊死
モデルにおいても化合物Ａの前処置により病変形成は有
意かつ用量依存的に抑制された。また、100mg/kg投与時
の病変形成抑制効果は極めて強力であり、抑制率は96％
に達した。 As is clear from the above table, in the gastric mucosal necrosis model with 0.6 N hydrochloric acid, the pretreatment with Compound A also significantly and dose-dependently suppressed the lesion formation. In addition, the effect of suppressing the formation of lesions at the dose of 100 mg / kg was extremely strong, with a suppression rate of 96%.
Reached.
上記の結果から明らかなように、化合物Ａを投与する
ことにより胃粘膜における壊死病変形成が有意かつ著明
に抑制された。このことから、化合物Ａが消化管粘膜保
護作用を有していることが明らかとなり、化合物Ａがす
ぐれた消化管疾患の予防及び治療効果を有することが確
認された。As is evident from the above results, administration of Compound A significantly and markedly suppressed the formation of necrotic lesions in the gastric mucosa. From this, it became clear that Compound A had a protective effect on gastrointestinal mucosa, and it was confirmed that Compound A had excellent preventive and therapeutic effects on gastrointestinal diseases.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 政安 裕之 東京都中央区八丁堀２丁目８番５号 第 一製薬株式会社内 審査官 岡部 義恵 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Hiroyuki Masayasu 2-8-5 Hatchobori, Chuo-ku, Tokyo Examiner, Daiichi Pharmaceutical Co., Ltd. Yoshie Okabe
Claims (1)
ール−３（2H）−オンまたはその生理学的許容塩を含有
する消化管疾患の予防および治療剤1. A preventive and therapeutic agent for gastrointestinal diseases containing 2-phenyl-1,2-benzisoselenazol-3 (2H) -one or a physiologically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29156387A JP2577016B2 (en) | 1987-11-18 | 1987-11-18 | Gastrointestinal disease treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29156387A JP2577016B2 (en) | 1987-11-18 | 1987-11-18 | Gastrointestinal disease treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01132522A JPH01132522A (en) | 1989-05-25 |
| JP2577016B2 true JP2577016B2 (en) | 1997-01-29 |
Family
ID=17770540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29156387A Expired - Fee Related JP2577016B2 (en) | 1987-11-18 | 1987-11-18 | Gastrointestinal disease treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2577016B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2553434B2 (en) * | 1992-04-28 | 1996-11-13 | 第一製薬株式会社 | Granular formulation |
| AU5513796A (en) * | 1995-04-25 | 1996-11-18 | Daiichi Pharmaceutical Co., Ltd. | Remedy for acquired immunodeficiency syndrome |
| AU3457300A (en) | 1999-03-31 | 2000-10-16 | Daiichi Pharmaceutical Co., Ltd. | Substrates for thioredoxin reductase |
| JP4887032B2 (en) * | 2005-11-25 | 2012-02-29 | 株式会社リコー | Packing equipment |
| US10058542B1 (en) | 2014-09-12 | 2018-08-28 | Thioredoxin Systems Ab | Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith |
| CN204806611U (en) * | 2015-06-26 | 2015-11-25 | 广东松下环境系统有限公司 | Heat exchange device |
-
1987
- 1987-11-18 JP JP29156387A patent/JP2577016B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01132522A (en) | 1989-05-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |